Hypothalamic tanycytes have been a cell type in search of a defined function for nearly sixty years. The prominent presence of tanycytes in the mediobasal hypothalamus, the key central regulator for a broad range of appetitive and emotional behaviors, has led to much speculation about their physiological function. A great deal of mostly indirect evidence has been accumulated to suggest their involvement in processes ranging from control of blood-brain barrier permeability, to regulation of neurohormone release and control of feeding, to adult neurogenesis. However, it has so far not been possible to effectively and selectively manipulate the function of tanycytes in vivo, and thus far these proposed functions of tanycytes have not been directed tested. We have identified a set of genes that are selectively expressed in hypothalamic tanycytes. We propose to use this data to generate transgenic mouse lines that will permit both selective and conditional ablation of tanycytes and selective and inducible Cre-based recombination in tanycytes. We will then selectively ablate hypothalamic tanycytes using these lines, and examine the contribution of these cells to aspects of hypothalamic physiology. PUBLIC HEALTH RELEVANCE: Hypothalamic tanycytes have been proposed to regulate many different physiological processes. However, it has thus far not been possible to effectively and selectively manipulate tanycyte function, and thus these proposed functions of tanycytes have not been directly tested. We propose to generate transgenic mice that will allow us to conditionally and selectively manipulate gene expression in hypothalamic tanycytes. We will use these lines to selectively ablate hypothalamic tanycytes and to study the behavior and physiology of mice lacking these cells.